Unfavorable outcome in CD15 negative pediatric classical Hodgkin lymphoma
1
Pediatr Blood Cancer 2008;50:430 LETTER TO THE EDITOR Unfavorable Outcome in CD15 Negative Pediatric Classical Hodgkin Lymphoma To the Editor: The letter of Barros et al. [1] raises interesting issues. In our study on pediatric Hodgkin lymphoma (HL), we found that lack of CD15 expression was independently associated with poor overall and poor failure-free survival (HL) [2]. Barros et al. reference to the study Petrella et al. [3] in which they have actually reported an unfavorable outcome of CD15 negative cases. Also, that study was done prior to when the distinction between classical HL and nodular lymphocyte predominant (LP) HL was described [4]. The latter is consistently CD15 negative, and has a significantly favorable outcome [5]. The report of Petrella et al. includes 11 cases of LP, which could have been either lymphocyte rich classical HL (one of the four classical HL subtypes) or nodular LP, and therefore cannot be compared with studies on CD15 negative classical HL. There are only two studies on classical HL which report CD15 negativity to be an independent prognostic factor for overall and disease-free/failure-free survival [2,6], while no prognostic significance is reported by many studies, possibly due to the limited number of cases studied. The German study included a large number of cases and is a good support for our findings, as they found a significant association between lack of CD15 expression and higher stages at diagnosis [6]. Other studies might confirm whether CD15 negative classical HL presents with unfavorable risk factors that would lead to a poorer survival. The significant association between CD15 negativity and p53 negativity reported in our paper refers to a total absence of p53 immunostaining, that is, absence of p53 overexpression. The same association was found between CD15 negativity and low p53 expression, with a cut-off value of 10% (P ¼ 0.009; odds ratio 5.4, 95% confidence interval 1.4–22). Wild-type p53 protein is normally below the detection sensitivity of immunohistochemistry. P53 immunodetection in Reed-Sternberg cells is thought to be the result of accumulation of a non-functional p53 protein, due to mdm2 binding, rather than p53 mutation [7]. However, Chabay et al. have shown that p53 is functional as a transcriptional activator in more than half the pediatric HL cases studied [7]. In any case, the association between loss of CD15 antigen expression and lack of p53 overexpression is a purely statistical correlation, which might be verified in further studies. The significant cut-off value for p53 expression in Reed-Sternberg cells is still to be identified. Veronique Dinand, MD, PhD* Department of Pediatrics All India Institute of Medical Sciences New Delhi, India Laxman S. Arya, MD Cancer Institute Indraprastha Apollo Hospital New Delhi, India Ramesh Dawar, MBBS, DABP , FICP Department of Pathology All India Institute of Medical Sciences New Delhi, India REFERENCES 1. Barros MHM, Zalcberg LR, Hassan R. Prognostic impact of CD15 expression and proliferative index in the outcome of children with classical Hodgkin lymphoma. Pediatr Blood Cancer 2007. 2. Dinand V, Malik A, Unni R, et al. Proliferative index and CD15 expression in pediatric classical Hodgkin lymphoma. Pediatr Blood Cancer 2007: [Epub ahead of print]. 3. Petrella T, Michiels R, Collin F, et al. CD15 antigen in Hodgkin’s disease. Pathol Res Pract 1989;185:886 –890. 4. Harris NL, Jaffe ES, Diebold J, et al. The World Health Organization classification of neoplasms of the hematopoietic and lymphoid tissues: Report of the Clinical Advisory Committee meeting—Airlie House, Virginia, November, 1997. Hematol J 2000;1:53–66. 5. Franklin J, Tesch H, Hansmann ML, et al. Lymphocyte predominant Hodgkin’s disease: Pathology and clinical implications. Ann Oncol 1998;9:S39–S44. 6. Elenita-Johnson KS, Medeiros J, Khorsan J, et al. P53 expression in Reed-Sternberg cells does not correlate with gene mutations in Hodgkin’s disease. Am J Clin Pathol 1996;106:728– 738. 7. Chabay P, Pesce P, De Matteo E, et al. No influence of bcl-2, p53 and p21waf1 protein expression on the outcome of pediatric Hodgkin lymphomas. J Pediatr Hematol Oncol 2006;28:552– 558. ß 2007 Wiley-Liss, Inc. DOI 10.1002/pbc.21371 —————— *Correspondence to: Veronique Dinand, Department of Pediatrics, Division of Pediatric Oncology, All India Institute of Medical Sciences, New Delhi 110 029, India. E-mail: [email protected] Received 16 August 2007; Accepted 16 August 2007
-
Upload
veronique-dinand -
Category
Documents
-
view
219 -
download
0
Transcript of Unfavorable outcome in CD15 negative pediatric classical Hodgkin lymphoma
Pediatr Blood Cancer 2008;50:430
LETTER TO THE EDITORUnfavorable Outcome in CD15 NegativePediatric Classical Hodgkin Lymphoma
To the Editor: The letter of Barros et al. [1] raises interesting
issues. In our study on pediatric Hodgkin lymphoma (HL), we found
that lack of CD15 expression was independently associated with
poor overall and poor failure-free survival (HL) [2].
Barros et al. reference to the study Petrella et al. [3] inwhich they
have actually reported an unfavorable outcome of CD15 negative
cases. Also, that study was done prior to when the distinction
between classical HL and nodular lymphocyte predominant (LP)
HL was described [4]. The latter is consistently CD15 negative, and
has a significantly favorable outcome [5]. The report of Petrella et al.
includes 11 cases of LP, which could have been either lymphocyte
rich classical HL (one of the four classical HL subtypes) or nodular
LP, and therefore cannot be compared with studies on CD15
negative classical HL. There are only two studies on classical HL
which report CD15 negativity to be an independent prognostic
factor for overall and disease-free/failure-free survival [2,6], while
no prognostic significance is reported bymany studies, possibly due
to the limited number of cases studied. TheGerman study included a
large number of cases and is a good support for our findings, as they
found a significant association between lack of CD15 expression
and higher stages at diagnosis [6]. Other studies might confirm
whether CD15 negative classical HL presents with unfavorable risk
factors that would lead to a poorer survival.
The significant association between CD15 negativity and p53
negativity reported in our paper refers to a total absence of p53
immunostaining, that is, absence of p53 overexpression. The same
association was found between CD15 negativity and low p53
expression, with a cut-off value of 10% (P¼ 0.009; odds ratio 5.4,
95%confidence interval 1.4–22).Wild-type p53 protein is normally
below the detection sensitivity of immunohistochemistry. P53
immunodetection in Reed-Sternberg cells is thought to be the result
of accumulation of a non-functional p53 protein, due to mdm2
binding, rather than p53 mutation [7]. However, Chabay et al. have
shown that p53 is functional as a transcriptional activator in more
than half the pediatric HL cases studied [7]. In any case, the
association between loss of CD15 antigen expression and lack of
p53 overexpression is a purely statistical correlation, which might
be verified in further studies. The significant cut-off value for p53
expression in Reed-Sternberg cells is still to be identified.
Veronique Dinand, MD, PhD*
Department of Pediatrics
All India Institute of Medical Sciences
New Delhi, India
Laxman S. Arya, MD
Cancer Institute
Indraprastha Apollo Hospital
New Delhi, India
Ramesh Dawar, MBBS, DABP, FICP
Department of Pathology
All India Institute of Medical Sciences
New Delhi, India
REFERENCES
1. Barros MHM, Zalcberg LR, Hassan R. Prognostic impact of CD15
expression and proliferative index in the outcome of children with
classical Hodgkin lymphoma. Pediatr Blood Cancer 2007.
2. Dinand V, Malik A, Unni R, et al. Proliferative index and CD15
expression in pediatric classical Hodgkin lymphoma. Pediatr Blood
Cancer 2007: [Epub ahead of print].
3. Petrella T, Michiels R, Collin F, et al. CD15 antigen in Hodgkin’s
disease. Pathol Res Pract 1989;185:886–890.
4. Harris NL, Jaffe ES, Diebold J, et al. TheWorld Health Organization
classification of neoplasms of the hematopoietic and lymphoid
tissues: Report of the Clinical Advisory Committee meeting—Airlie
House, Virginia, November, 1997. Hematol J 2000;1:53–66.
5. Franklin J, Tesch H, HansmannML, et al. Lymphocyte predominant
Hodgkin’s disease: Pathology and clinical implications. Ann Oncol
1998;9:S39–S44.
6. Elenita-Johnson KS, Medeiros J, Khorsan J, et al. P53 expression in
Reed-Sternberg cells does not correlate with gene mutations in
Hodgkin’s disease. Am J Clin Pathol 1996;106:728–738.
7. Chabay P, Pesce P, De Matteo E, et al. No influence of bcl-2,
p53 and p21waf1 protein expression on the outcome of pediatric
Hodgkin lymphomas. J Pediatr Hematol Oncol 2006;28:552–
558.
� 2007 Wiley-Liss, Inc.DOI 10.1002/pbc.21371
——————*Correspondence to: Veronique Dinand, Department of Pediatrics,
Division of Pediatric Oncology, All India Institute of Medical
Sciences, New Delhi 110 029, India. E-mail: [email protected]
Received 16 August 2007; Accepted 16 August 2007
